Prenatal stress alters amygdala functional connectivity in preterm neonates

Abstract

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders.We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used.When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth.Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

Somatosensory function and pain in extremely preterm young adults from the UK EPICure cohort: sex-dependent differences and impact of neonatal surgery

“… 54 More specifically, differences in amygdala volume and connectivity influenced fear processing and emotion recognition after preterm birth. 55 , 56 , 57 , 58 Here, amygdala volume correlated with both the degree and directionality of altered thermal sensitivity (i.e. decreased in males, increased in females).…”

What Do We Know About the Preterm Behavioral Phenotype? A Narrative Review

“…ASD and social-communicative problems have also been associated with brain abnormalities as defined by reductions in total cerebral volume (44) and in volumes of the frontal, occipital, and limbic regions (45,46), as well as periventricular leukomalacia (47), and other white matter abnormalities (44). Similarly, a potential explanation for increased anxiety and internalizing problems in the preterm population include white matter abnormalities (43) and reduced volume and connectivity in the amygdala (48)(49)(50)(51). While there is support for neurological correlates of ADHD, ASD, and anxiety in the preterm population independently, there is little evidence to support brain mechanisms of comorbid psychopathology.…”

Association of Prenatal Maternal Psychological Distress With Fetal Brain Growth, Metabolism, and Cortical Maturation

“…These findings have included smaller head circumference, 13 reduced cerebral and cerebellar gray matter volume, [16][17][18] increased amygdala 19,20 and decreased hippocampal volumes, 21 and altered brain microstructure 22,23 and connectivity. 24,25 Furthermore, disturbances in brain biochemicals have been reported in animal studies, including reductions in N-acetylaspartate (NAA; a marker of neuronal integrity) in the frontal cortex and hypothalamus in early life stress-exposed mice [26][27][28] as well as altered neurotransmitter metabolism of γ-aminobutyric acid and glutamate in the right hippocampus of pregestational stress-exposed offspring. 29 Although a growing body of evidence finds a correlation between prenatal maternal psychological distress and neurodevelopmental dysfunction in their offspring, the association of psychological distress with fetal brain development and metabolism remains poorly understood at this time.…”